Disposable urea sensor and system for determining creatinine and urea nitrogen-to-creatinine ratio in a single device

Abstract

A disposable urea sensor has a laminated body having a fluid sample inlet end and an electrical contact end, a fluid sample inlet, a substantially flat sample chamber in communication between the fluid sample inlet and a vent opening, the sample chamber being adapted to collect a fluid sample through the fluid sample inlet, a working electrode and a reference electrode within the sample chamber, and a reagent matrix disposed on the working electrode wherein the reagent matrix contains urease.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The present invention relates generally to electrochemical sensors that can be used for the quantification of a specific component or analyte in a liquid sample. Particularly, the present invention relates to a disposable electrochemical sensor for measuring urea (or BUN, Blood Urea Nitrogen) in biological fluids such as blood. More particularly, the present invention relates to a system for simultaneously determining creatinine and BUN-to-creatinine ratio in a single device. Still more particularly, the present invention relates to a device that can be employed to perform assays of urea, creatinine and blood urea nitrogen-to-creatinine ratio in a small volume liquid sample (around 1 μL). [0003] 2. Description of the Prior Art [0004] In the liver, urea is synthesized from ammonia produced as a result of de-amination of amino acids. This biosynthetic pathway is the main means of disposal of excess nitrogen by the bod...

AI Technical Summary

Benefits of technology

[0016] It is an object of the present invention to provide a disposable urea sensor capable of measuring the urea concentration in a small volume of body fluid. It is another object of the present invention to provide a disposable urea sensor that is capable of measuring the urea concentration in a small volume of body fluid such as blood obtained by lancing the skin of the user. It is a further object of the present invention to provide a disposable urea sensor that has a fast response time. It is yet another object of the present invention to provide a disposable sensor for use in determining urea, creatinine and BUN-to-creatinine ratio in a body fluid sample. It is still another object of the present invention to provide a system for determining urea, creatinine and BUN-to-creatinine ratio in a blood sample with a single disposable device.

[0023] In yet another aspect of the first embodiment, the laminated body of the present invention has a top layer with a vent opening and preferably an entrance notch. The vent opening is located such that at least a portion of the vent opening overlays the bottom of the U-shaped cutout of the second middle insulating layer. The vent allows air within the sample fluid channel to escape as the sample fluid enters the sample entrance end of the laminated body. The notch is located at the sample entrance end. The sample fluid generally fills the sample fluid channel by capillary action. In small volume situations, the extent of capillary action is dependent on the hydrophobic / hydrophilic nature of the surfaces in contact with the fluid undergoing capillary action. Capillary forces are enhanced by either using a hydrophilic insulating material to form the top layer, or by coating at least a portion of one side of a hydrophobic insulating material with a hydrophilic substance in the area of the top layer that faces the sample fluid channel between the sample entrance end of the laminated body and the vent opening of the top layer. It should be understood that an entire side of the top layer may be coated with the hydrophilic substance and then bonded to the second middle layer.

[0027] In the second embodiment of the present invention, the sensor of the present invention has a similar structure to the first embodiment, but it has one working electrode, one reference electrode and one blank electrode. The working electrode is loaded with a urea sensitive enzyme (urease) and other ingredients; the blank electrode is loaded with a similar chemistry except without adding a urea sensitive enzyme. Such a three-electrode system not only possesses the feature of the first embodiment, but also the capability of eliminating interference from any oxidizable species in the sample, such as ascorbic acid, acetaminophen, uric acid, etc.

[0038] In another aspect of the fifth embodiment, the first working electrode (W1) is loaded with a urea sensitive enzyme (urease) and other ingredients; the second working electrode (W2) is loaded with creatinine / creatine sensitive enzymes and other ingredients; the third working electrode (W3) is loaded with creatine sensitive enzymes and other ingredients; the blank electrode (B) is preferably loaded with the same chemistry as W1 without adding any enzyme. Such a five-electrode system (including the reference electrode), in a single device, not only possesses the feature of the second embodiment, having the capability of eliminating interference from any oxidizable species in the sample, but also possesses the capability of measurement of creatinine and blood urea nitrogen-to-creatinine ratio.

Problems solved by technology

High urea concentration in blood is toxic to the body.

Malfunctioning kidneys will have difficulty in getting rid of the excess urea.

None of the previous approaches, however, describes a combination of disposable, small volume, mass fabricated sensors with dissolvable reagent matrix containing the enzyme urease.

The prior known sensors have not enabled the desired point-of-care blood test for blood urea, thereby assuring that the procedure was complete.

On the other hand, a low BUN value may be caused by a diet very low in protein, malnutrition, or severe liver damage.

Drinking excessive amounts of liquid may cause overhydration and lead to a low BUN value.

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